Background/Aims:Real-world evidence for upadacitinib use in strictly defined difficult-to-treat Crohn's disease (DTT-CD), particularly in Asian populations, remains limited. Herein, we aimed to evaluate the efficacy and safety of upadacitinib in Chinese patients with DTT-CD. Methods:This multicenter, bidirectional cohort study was conducted at 8 Chinese inflammatory bowel disease centers. Patients received upadacitinib 45 mg once daily for 12 weeks induction, followed by 15 mg daily for maintenance. The coprimary endpoints were clinical remission at week 12 and week 24. Results:Among the 151 DTT-CD patients enrolled, the clinical remission rates were 47.0% at week 12 and 62.9% at week 24, with endoscopic remission achieved in 28.1% of patients at week 24. Adverse events occurred in 42 (27.8%) during induction and in 33 (21.9%) during maintenance, with 3 serious events (venous thrombosis, perforation, and hemorrhage) reported during the maintenance phase. Notably, 2 male reproductive system-related adverse events were observed, including blue semen in 2 patients and a suspected case of paternal teratogenicity with fetal anomalies and pregnancy loss. The drug persistence at week 24 was 93.4%. Conclusions:Upadacitinib demonstrated robust efficacy in Chinese patients with DTT-CD, with a manageable safety profile and high treatment persistence.

Life-course body size dynamics may contribute to inflammatory bowel disease (IBD) risk, but whether distinct anthropometric trajectories add information beyond adult body mass index (BMI) and inherited susceptibility remains unclear. We included 486,449 UK Biobank participants free of IBD at baseline; trajectory analyses were restricted to 262,601 participants with complete self-reported birth weight, recalled childhood body size at age 10 years, and measured baseline BMI, and joint trajectory–polygenic risk score (PRS) analyses included 254,481 participants with complete trajectory and PRS data. During a median follow-up of 14.7 years, 1,722 participants developed Crohn’s disease (CD) and 3,340 developed ulcerative colitis (UC) in the eligible cohort. Group-based trajectory modelling identified five trajectories. Compared with the stable Normal–Average–Normal trajectory, Normal–Thinner–Overweight/obesity and Macrosomia–Average–Overweight/obesity showed modest nominal associations with higher UC risk, whereas comparable associations were not observed for CD. In PRS-stratified trajectory analyses, relative hazard ratios for UC appeared elevated for several non-reference trajectories in the low-PRS stratum, but estimates were imprecise because of sparse events in the reference cell and absolute risk differences were modest. These findings provide hypothesis-generating evidence that life-course body-size patterning may be related to adult-onset UC more than CD, but interpretation is limited by missing trajectory data, retrospective recall of early-life body size, multiple testing, sparse stratified events, and health-record-based outcome ascertainment.

Background/Aims:This study aimed to investigate the prognostic value of early post-induction intestinal ultrasound (IUS) findings in predicting long-term clinical outcomes among patients with moderate-to-severe ulcerative colitis (UC). Methods:This retrospective, single-center study consecutively enrolled patients with moderate-to-severe, left-sided or extensive UC. Clinical endpoints were assessed at the end of follow-up or 1 year after induction therapy (for patients with at least 1 year of follow-up) and categorized as clinical remission (Short Clinical Colitis Activity Index [SCCAI] ≤ 2) or non-remission (SCCAI > 2). Patients who experienced a negative disease course before the evaluation point were classified as clinical non-remission. Results:A total of 56 patients were included. The bowel wall thickness (BWT; 5.1 ± 1.7 mm vs. 6.0 ±1.4 mm; P= 0.032) and Milan ultrasound criteria (MUC; 8.3 ± 3.2 vs. 9.9 ± 2.2; P= 0.029) evaluated at early follow-up IUS were lower for patients reaching longterm clinical remission. Patients with BWT < 5 mm on early follow-up IUS (83% vs. 45%; P= 0.006) or MUC < 6.2 (100% vs. 45%; P< 0.001) had a significantly higher rate of long-term clinical remission. Kaplan-Meier analysis revealed a lower cumulative probability of a negative disease course in patients with BWT < 5 mm (P= 0.025) or MUC < 6.2 (P= 0.025). Cox regression analysis identified BWT ≥ 5 mm as an independent predictor of a negative disease course. Conclusions:BWT <5 mm and MUC < 6.2 may serve as intermediate targets for IUS-guided "treat-to-target" strategy, offering a practical approach to improve longterm clinical remission in patients with moderate-to-severe UC.

Cronkhite–Canada syndrome (CCS) is a rare non-inherited hamartomatous polyposis syndrome with unknown pathogenesis. To investigate this, we performed single-cell RNA sequencing, spatial in situ sequencing, and bulk RNA-seq on colon biopsies from CCS patients and healthy controls, along with cytokine profiling and organoid/cell line experiments. Multi-omics analysis revealed goblet cell hyperplasia and increased mucin secretion, spatially associated with an inflammatory niche consisting of TNF⁺ Th1 cells, FCN1+ monocytes, and IL1B+ macrophages, all highly active in CCS. Functional assays showed that low-dose TNF-α drives monocyte differentiation into IL-1β-secreting macrophages, while IL-1β induces epithelial PGE2 production, which further amplifies IL-1β secretion, establishing a self-reinforcing loop. An independent cohort confirmed mild elevation of peripheral TNF-α and TNF/IL-1 pathway activation. These findings delineate a pathogenic circuit linking adaptive immune dysregulation, innate remodeling, and epithelial changes, positioning the TNF-α/IL-1β/PGE2 axis as the driver of mucus accumulation and hamartoma formation, offering new potential therapies for CCS. Key features distinguishing Cronkhite–Canada syndrome (CCS) hamartomatous polyps from healthy intestinal tissues and crosstalk among CD4+ T-helper 1 TNF+ cells, FCN1+ monocytes, IL1B+ macrophages, and altered epithelial lineage establish a unique immune microenvironment in CCS. This interaction network drives the accumulation of mucus and remodeling of epithelial lineages via paracrine signaling (e.g., TNF-α/IL-1β/PGE2 axis), collectively forming a pathogenic triad that underpins the development of CCS lesions.

ObjectiveTo investigate the molecular mechanism by which fecal microbiota transplantation (FMT) alleviates gastrointestinal inflammation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine acute graft-versus-host disease (aGVHD).MethodsA murine aGVHD model after allo-HSCT was established, and BALB/c mice were randomly assigned to blank control, bone marrow transplantation, aGVHD model, and FMT treatment groups (n=6 per group). Disease severity was assessed by histopathology. Expression of receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was evaluated by immunohistochemistry. Protein levels of RIPK1, RIPK3, MLKL, phosphorylated RIPK1 (p-RIPK1), and phosphorylated MLKL (p-MLKL) were determined by Western blotting. Plasma regenerating islet-derived protein 3 alpha (Reg3α) was measured by enzyme-linked immunosorbent assay. The intestinal microbiota was profiled by 16S rRNA gene sequencing.ResultsCompared with the aGVHD model group, the FMT group showed higher relative abundances of Firmicutes and Bacteroidetes and a lower relative abundance of Proteobacteria; body weight loss was markedly attenuated, and survival time was prolonged. Alpha-diversity indices (Simpson, Pielou, Shannon) increased in the FMT group (P<0.05). Intestinal pathology scores, expression of RIPK1, RIPK3, and MLKL, protein levels of RIPK1, RIPK3, MLKL, p-RIPK1, and p-MLKL, and plasma Reg3α levels were significantly reduced in the FMT group versus the aGVHD model group (all P<0.05).ConclusionsFMT may attenuate gastrointestinal inflammation in aGVHD by restoring intestinal microbial balance and inhibiting the RIPK1/RIPK3-mediated necroptosis pathway.

Background: Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a rare disease characterized by multiple small intestinal ulcers whose pathogenesis remains poorly understood. This study aimed to characterize the proteomic and phosphoproteomic profiles of CEAS and to identify molecular pathways involved in its pathogenesis. Methods: Quantitative proteomics and phosphoproteomics were performed on intestinal mucosal tissues from patients with CEAS (n = 3), Crohn’s disease (CD, n = 3), and healthy controls (n = 3). Differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) were analyzed using functional enrichment, gene set enrichment analysis (GSEA), protein–protein interaction (PPI) networks, and integrative analysis. Results: A total of 900 DEPs were identified in CEAS and 277 in CD relative to controls, including 717 CEAS-specific proteins. CEAS-specific alterations were strongly enriched in focal adhesion and extracellular matrix-related pathways, whereas shared proteins between CEAS and CD were primarily associated with epithelial barrier function, including tight junction and adherens junction pathways. GSEA revealed that CEAS was characterized by upregulation of tissue remodeling and focal adhesion pathways, accompanied by suppression of digestive and metabolic processes, while CD exhibited prominent adaptive immune activation. PPI network analysis identified POSTN, CDH1, TLN1, and VIM as candidate hub proteins; however, none retained significance after FDR correction, whereas brush-border components (CDHR2, MUC3A, MUC13, ALPI) and actin cytoskeletal regulators remained the most statistically robust alterations. Integrated analysis further highlighted focal adhesion-related proteins with coordinated expression and phosphorylation changes. Conclusions: This exploratory study provides the first integrative proteomic and phosphoproteomic characterization of CEAS, suggesting that impairment of the intestinal brush border and mucosal barrier, together with actin cytoskeletal reorganization, may distinguish CEAS from immune-dominant CD. These findings are hypothesis-generating and require validation in larger cohorts.

BACKGROUND/AIMS:The awareness, accessibility, and utilization of transabdominal intestinal ultrasound (IUS) in inflammatory bowel disease (IBD) management from both physicians' and patients' perspectives remains unclear in China. This nationwide cross-sectional survey aimed to gauge the current utilization of IUS, physician and patient perceptions and knowledge gap in IBD management across China. METHODS:A structured questionnaire, developed by the China IUS Group, was distributed to 612 physicians (69.8% of gastroenterologists, 28.0% of radiologists) from 38 tertiary hospitals and 1,154 IBD patients. RESULTS:A total of 91.7% of physicians expressed an intention to incorporate IUS into future clinical practice. However, while 69.3% of physicians reported IUS availability at their institutions, its utilization varied widely. Only 16.5% of physicians applied IUS to more than 75% of their IBD patients. Additionally, 27.1% of physicians reported receiving IUS training. Radiologists were more likely than gastroenterologists to consider IUS as a sensitive tool for evaluating treatment efficacy (48.3% vs. 19.4%, P< 0.001), intestinal wall fibrosis (33.7% vs. 27.4%, P< 0.001), intestinal fistula (27.9% vs. 11.2%, P< 0.001), abdominal abscesses (49.4% vs. 28.6%, P< 0.001), and disease severity (30.2% vs. 11.0%, P< 0.001). Patients expressed high satisfaction with IUS (76.1%), yet 39.2% had safety concerns. CONCLUSIONS:Despite growing recognition of IUS in China, its wide utilization in IBD management requires further promotion. The notable disparity between gastroenterologists and radiologists regarding IUS underscores the need for targeted, specialty-specific training. Strengthening patient education efforts is essential to further enhance patient acceptance of IUS.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Crohn's disease (CD) is frequently complicated by intestinal strictures, which substantially affect patients quality of life and long-term outcomes. Accurate classification of strictures-as inflammatory, fibrotic, or mixed-is critical for selecting optimal therapeutic strategies. In clinical practice, multidisciplinary team (MDT) consultation is often employed to assess stricture characteristics. However, the accuracy and inter-specialty consistency of stricture evaluation within MDTs remain inadequately characterized. This study aimed to assess the intra-disciplinary consistency and accuracy of decision-making for CD-related strictures, evaluate the accuracy of post MDT decisions, and propose recommendations for stricture nature assessment and MDT workflow optimization. A mixed-methods study was conducted at Peking Union Medical College Hospital involving 42 patients with CD and intestinal strictures. MDT participants-including specialists from gastroenterology, surgery, ultrasound, and MDT meeting chairs-were involved in evaluating intra-disciplinary decision consistency and accuracy. Semi-structured qualitative interviews were also conducted to explore factors influencing clinical decision-making. Gastroenterologists demonstrated the highest intra-team consistency (PABAK = 0.75) and diagnostic accuracy (89.3%). Ultrasound specialists showed improved consistency following targeted training (from 0.46 to 0.93). The overall accuracy of historical MDT decisions was 92.9%. Key factors influencing stricture nature judgment included clinical presentation, laboratory findings, imaging features, and endoscopic evaluation. Seven core components were identified to improve MDT workflow: expert selection, team building, training, pre-meeting preparation, in-meeting procedures, post-meeting actions, and continuous quality improvement. This study reveals variability in decision-making for CD-related strictures across different specialties. To improve diagnostic accuracy and treatment planning, we propose clear stricture classification criteria and a structured MDT workflow to standardize and enhance multidisciplinary management of CD.

PurposeWe aimed to perform a Bayesian network meta-analysis to assess the comparative diagnostic performance of different imaging modalities in chronic pancreatitis(CP).MethodsThe PubMed, Embase and Cochrane Library databases were searched for relevant publications until March 2024. All studies evaluating the head-to-head diagnostic performance of imaging modalities in CP were included. Bayesian network meta-analysis was performed to compare the sensitivity and specificity between the imaging modalities. The Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool was used to evaluate the quality of studies.ResultsThis meta-analysis incorporated 17 studies. Network meta-analytic results indicated that endoscopic ultrasonography (EUS) achieved the highest surface under the cumulative ranking (SUCRA) value at 0.86 for sensitivity. Conversely, magnetic resonance imaging (MRI) demonstrated best specificity, recording the highest SUCRA value at 0.99. Ultrasonography (US) displayed comparatively lower sensitivity than endoscopic retrograde cholangiopancreatography (ERCP) (relative risk[RR]: 0.83, 95% Confidence Interval[CI]: 0.69-0.99) and EUS (RR: 0.73, 95% CI: 0.57-0.91). MRI outperformed all other imaging modalities in terms of specificity.ConclusionsIt appears that EUS demonstrates higher sensitivity, while MRI exhibits higher specificity in patients with chronic pancreatitis. However, it is crucial to note that our analysis was limited to the diagnostic performance and did not evaluate the cost-effectiveness of these various imaging modalities. Consequently, further extensive studies are needed to assess the benefit-to-risk ratios comprehensively.

Background: Patients with inflammatory bowel disease (IBD) have an elevated colorectal cancer (CRC) risk, though the etiology remains unclear. This study aimed to elucidate the interplay among IBD, gut microbiota (GM), inflammatory biomarkers, and CRC risk. Methods: First, we employed cohort analysis using the UK Biobank (UKB), linkage disequilibrium score regression (LDSC), and Mendelian randomization (MR) analyses to investigate the association between IBD and CRC. Second, inflammatory biomarkers' indirect effect was assessed using mediation analysis. Third, the causal effects of IBD on GM and GM on inflammatory biomarkers were evaluated using MR. Finally, we constructed a disease severity biomarker score and evaluated its CRC risk stratification performance. Results: Among 441,321 participants, IBD was associated with a 1.78-fold (95% confidence interval (CI): 1.45-2.18) increased risk of CRC. While LDSC and MR analyses showed no genetic correlation between IBD and CRC, mediation analyses revealed that C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) significantly mediated 10.41% and 9.97% of the IBD-CRC association, respectively. IBD increased the GM abundance of Rikenellaceae RC9 gut group, and decreased Lactobacillaceae and Ruminococcus 2, which in turn affected CRP, neutrophils, and lymphocytes. Notably, IBD decreased the abundance of Ruminococcus 2 after Bonferroni correction (β = -9.463, p=0.0002). A disease severity biomarker score comprising of CRP, platelets, platelet-to-lymphocyte ratio (PLR), NLR, hemoglobin (Hgb), and albumin was constructed. IBD patients with the highest scores had a 3.07-fold (95% CI: 1.35-7.00) higher CRC risk compared to those with the lowest scores. Conclusions: IBD alters the microbial abundance of Rikenellaceae RC9 gut group, Lactobacillaceae, and Ruminococcus 2, thereby, influencing inflammatory biomarkers including CRP, neutrophils, and lymphocytes, which mediate the increased risk of CRC in IBD patients. The constructed biomarker score enables individualized CRC risk stratification in IBD patients.

Liquid–liquid phase separation (LLPS) is an emerging research field in cellular biology. LLPS-driven biomolecular condensates act as reaction chambers and regulatory hubs for critical processes, including chromatin architecture, gene expression, and metabolism. The dysregulation of these processes frequently impedes the proper execution of physiological functions. Current research indicates that abnormal phase separation plays a significant role in the pathogenesis of diseases and aging. This review briefly overviews the fundamental concepts and research methods related to phase separation. We also summarize studies concerning its physiological functions, particularly emphasizing its role in hematopoiesis. We further discuss how abnormal phase separation can lead to hematological disorders, specifically summarizing its involvement in the pathogenesis of leukemia. Despite recent advancements, elucidating LLPS mechanisms in hematopoiesis remains challenging due to the intricate interplay between biomolecular condensates and cellular function. Future research efforts aiming to reveal the role of LLPS in hematological diseases hold promise for novel therapeutic interventions and a deeper understanding of hematopoietic processes.

Background: Disease extent of ulcerative colitis (UC) is dynamic, often shows progression or regression over time. However, factors associated with disease progression in long-term follow-ups remain underexplored. Objectives: This study aimed to examine disease extent progression in Chinese patients in a long-term follow-up cohort and identify associated risk factors. Design: Retrospective analysis. Methods: We retrospectively analyzed 800 hospitalized UC patients from 1980 to 2021, and followed up to December 2023. The disease extent was categorized according to the Montreal classification. The Cox regression model was used to identify factors associated with progression. Results: At diagnosis, 19.1% had E1 (ulcerative proctitis), 29.8% had E2 (left-sided UC), and 51.1% had E3 (extensive UC). By the end of follow-up, the proportion of maximum disease extent of E3 cases increased to 74.9%, while E1 and E2 patients decreased to 6.6% and 18.5%, respectively. Cox regression analysis revealed that patients with a history of appendectomy before the onset of disease were at higher risk of disease progression in those initially diagnosed with E1. Lower usage of glucocorticoids, immunosuppressants, and biologics were found in progression to the E3 group than initial E3 group. Lower usage of immunosuppressants and biologics before progression were found in the progressed to E3 group than not progressed to E3 group. Conclusion: Disease extent progression was common in Chinese UC patients. We suggest the necessity of aggressive treatment strategies, especially for early-stage UC patients, to mitigate disease progression and reduce the risk of related complications.

Bile reflux gastritis (BRG) may lead to precancerous lesions of gastric cancer and gastric cancer. Although ursodeoxycholic acid (UDCA) has been used to treat BRG, its clinical efficacy remains unknown. Therefore, we systematically evaluated the efficacy and safety of UDCA compared with conventional therapy for BRG. We selected candidate studies and generated a forest plot to evaluate outcomes. Metaregression analysis was conducted to identify possible explanations for heterogeneity. Study quality was evaluated using the Cochrane Risk of Bias 2 tool and the Newcastle–Ottawa scale. The quality of evidence for the outcomes of the meta-analysis was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. A total of 14 studies including 1605 patients were identified. Compared with control groups, medication combined with UDCA significantly reduced the number of reflux episodes [mean difference (MD) = − 17.99 times, 95